It is well known that the spinal motor nerve exerts trophic influences on skeletal muscle. Evidence indicates that such trophic influences are mediated in part by trophic substances released by the nerve. This laboratory has isolated and substantially purified an 84,000 dalton protein from adult sciatic nerves which exerts trophic influences on muscle cells in vitro. This proposal is designed to further purify and characterize the active protein, and to study its localization in motor nerves and its mechanism of action in situ. The proposed project will provide definitive evidence for the chemical nature of trophic substance(s) released by nerves.